Immunogenic composition comprising Panton-Valentine Leukocidin (PVL) derived polypeptides
View Patent ↗The present disclosure provides immunogenic compositions useful in prevention and treatment of Staphylococcus aureus infection. In particular, the disclosure provides methods of inducing an immune response against a panton-valentine leukocidin (PVL)-expressing S. aureus , methods of preventing or treating S. aureus infections, and composition for preventing or treating S. aureus infections.
1. An isolated mutant staphylococcal leukocidin subunit polypeptide comprising a wild-type staphylococcal leukocidin subunit except for one to five amino acid substitutions at conserved residues, which reduce toxicity of the mutant leukocidin subunit relative to the corresponding wild-type leukocidin subunit;
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 6 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K97 of SEQ ID NO: 6,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 15 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K125of SEQ ID NO: 15,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 17 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K102 of SEQ ID NO: 17,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 21 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K126 of SEQ ID NO: 21,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 22 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K126 of SEQ ID NO: 22,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 23 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K126 of SEQ ID NO: 23,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 24 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K128 of SEQ ID NO: 24,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 25 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K128 of SEQ ID NO: 25,
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 26 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K128 of SEQ ID NO: 26, or
wherein the wild-type leukocidin subunit comprises the amino acid sequence SEQ ID NO: 27 and wherein the mutant staphylococcal leukocidin subunit polypeptide comprises an amino acid substitution at a position corresponding to K128 of SEQ ID NO: 27.
2. The mutant leukocidin subunit of claim 1 , wherein the wild-type leukocidin subunit is a Panton-Valentine leukocidin (PVL) LukS-PV comprising the amino acid sequence SEQ ID NO: 6.
3. The mutant leukocidin subunit of claim 2 , wherein the subunit comprises the amino acid sequence SEQ ID NO: 7 or SEQ ID NO: 14.
4. The mutant leukocidin subunit of claim 3 comprising the amino acid sequence SEQ ID NO: 14.
5. The mutant leukocidin subunit of claim 1 , wherein the wild-type leukocidin subunit is a Panton-Valentine leukocidin (PVL) LukF-PV comprising the amino acid sequence SEQ ID NO: 17.
6. The mutant leukocidin subunit of claim 5 , wherein the subunit comprises the amino acid sequence SEQ ID NO: 18 or SEQ ID NO: 136.
7. The mutant leukocidin subunit of claim 6 comprising the amino acid sequence SEQ ID NO: 18.
8. A composition comprising the mutant leukocidin subunit of claim 1 and a carrier.
9. A method of inducing a host immune response against a Staphylococcus aureus strain, comprising administering to a subject in need of the immune response an effective amount of the composition of claim 8 .
10. The mutant leukocidin subunit of claim 6 comprising the amino acid sequence SEQ ID NO: 136.
11. A composition comprising the mutant leukocidin subunit of claim 6 and a carrier.
12. A method of inducing a host immune response against a Staphylococcus aureus strain, comprising administering to a subject in need of the immune response an effective amount of the composition of claim 11 .
13. A composition comprising the mutant leukocidin subunit of claim 3 and a carrier.
14. A method of inducing a host immune response against a Staphylococcus aureus strain, comprising administering to a subject in need of the immune response an effective amount of the composition of claim 13 .
15. A composition comprising the mutant leukocidin subunit of claim 4 and a carrier.
16. A method of inducing a host immune response against a Staphylococcus aureus strain, comprising administering to a subject in need of the immune response an effective amount of the composition of claim 15 .
17. A composition comprising the mutant leukocidin subunit of claim 7 and a carrier.
18. A method of inducing a host immune response against a Staphylococcus aureus strain, comprising administering to a subject in need of the immune response an effective amount of the composition of claim 17 .
19. A composition comprising the mutant leukocidin subunit of claim 10 and a carrier.
20. A method of inducing a host immune response against a Staphylococcus aureus strain, comprising administering to a subject in need of the immune response an effective amount of the composition of claim 19 .
21. The mutant leukocidin subunit of claim 1 , wherein the substituted wild-type lysine (K) is substituted with an alanine (A).